Host microbiota modulates development of social preference in mice

Abstract

BackgroundMounting evidence indicates that the indigenous gut microbiota exerts long-lasting programming effects on brain function and behaviour.ObjectiveIn this study, we used the germ-free (GF) mouse model, devoid of any microbiota throughout development, to assess the influence of the indigenous microbiota on social preference and repetitive behaviours (e.g. self-grooming).Methods and resultsUsing the three-chambered social approach task, we demonstrate that when adult GF mice were given a choice to spend time with a novel mouse or object, they spent significantly more time sniffing and interacting with the stimulus mouse compared to conventionally raised mice (specific pathogen-free, SPF). Time spent in repetitive self-grooming behaviour, however, did not differ between GF and SPF mice. Real-time PCR–based gene expression analysis of the amygdala, a key region that is part of the social brain network, revealed a significant reduction in the mRNA levels of total brain-derived neurotrophic factor (BDNF), BDNF exon I-, IV-, VI-, IX-containing transcripts, and NGFI-A (a signalling molecule downstream of BDNF) in GF mice compared to SPF mice.ConclusionThese results suggest that differential regulation of BDNF exon transcripts in the amygdala by the indigenous microbes may contribute to the altered social development of GF mice.

Kynurenine pathway metabolism and the microbiota-gut-brain axis

“…Such studies have demonstrated, with relative consistency, that the gut microbiota modulates anxiety (Arentsen et al, 2015;Clarke et al, 2013;Diaz Heijtz et al, 2011;Neufeld et al, 2011;Savignac et al, 2014) and depressive like behaviour (Bravo et al, 2011;Desbonnet et al, 2015;Desbonnet et al, 2008;Messaoudi et al, 2011;Wong et al, 2016). Of particular note is a study showing that an anxiety-like phenotype can be transferred from one mouse strain to another by faecal microbiota transplant (Bercik et al, 2011).…”

“…GF animals exhibit altered social novelty preference-a natural social behaviour expressed by conventional mice- (Arentsen et al, 2015;Desbonnet et al, 2014) which can be normalised if bacterial colonisation occurs post-weaning (Desbonnet et al, 2014). The maternal immune activation mouse model has been utilised to investigate, pre-clinically, neurodevelopmental disorders such as autism spectrum disorders which are characterised by marked social and communication difficulties (Carr, 2006).…”

Gutsy Moves: The Amygdala as a Critical Node in Microbiota to Brain Signaling

“…Like humans, rodents are naturally social animals, but GF rats and mice exhibit deficits in social behaviors such that they show less interest in social interaction and poorer memory for social partners. [89,[110][111][112] Deficits in social behavior are also observed following antibiotic-induced depletion of the microbiota. [72,113] The microbiota also plays a role in murine models of ASD, where treatment with specific bacteria has been shown to reverse many of the social deficits observed in these animals.…”

Gut Microbiota and Anxiety: An Exploration of Key Findings

“…Consistent with the exaggerated stress response in GF animals, the absence of gut microbiota in rodent model exacerbates the neuroendocrine and behavioral response to acute stress [11]. Studies have shown that GF mice exhibit a reduction in basal levels of anxiety like behaviors as compared to mice with a normal gut microbiota [8,12,13]. Moreover, anxiety-like behaviors of GF mice are unaffected by maternal separation, pointing towards the role of the gut microbiota in the induction of the anxiety response associated with early life stress [14].…”